AB1252 RETROSPECTIVE SINGLE CENTER STUDY OF THE PREDICTIVE ROLE OF CERTAIN BIOMARKERS IN MACROPHAGE ACTIVATION SYNDROME RELATED TO SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS
Authors: M. Kaleda, E. Fedorov, I. Nikishina, S. Salugina, V. Matkava, M. Cherkasova, E. Samarkina
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic juvenile idiopathic arthritis (sJIA) is a childhood arthritis with signs of autoinflammation and high risk of macrophage activation syndrome (MAS). Immunopathogenesis of sJIA is based on excessive activation of innate immunity, which is characterized by hyperproduction of pro-inflammatory cytokines - interleukin (IL)-1 and IL-18, which play a key role in induction of synthesis of other pro-inflammatory mediators. Macrophage activation mediates the evidence of hyperferritinemia, which stimulates a pathological immune response with the development of MAS. In clinical practice, the study of the cytokine profile and its comparison with the acute-phase inflammatory response markers in patients (pts) with sJIA can make possible assessment the nature of the course process and predict the possibility of MAS. Objectives To study distinctive features of some biomarkers in pts with sJA in relation with history of MAS. Methods Total IL-18, IP-10, IL1RA, IL1b, IL6, CRP and ferritin levels were determined in pts with sJIA and compared between between groups regarding to disease activity and history of MAS. Serum levels of cytokines, ferritin were measured using standard commercial enzyme-linked immuno-sorbent assay. CRP were estimated by commercial nephelometric method. Results A total of 39 pts were included to study, the ratio of boys and girls was 1:1.4. Median age of sJIA onset was 4.4 years [2.9; 6.5], age at the time of examination - 11.4 years [7.35; 13.5]. The pts were divided into 3 groups: group I - with MAS (8 pts), group II - with active sJIA without MAS (16 pts), group III - with inactive sJIA (15 pts). Total IL-18 levels were significantly higher in pts with MAS (group I) (median 6036.5 pg/ml [IQR 1932.5; 9160.3], and remained persistently elevated even in the majority of pts with inactive disease (group III) (median 1625.25 pg/ml [IQR 634.1; 2451.6]. CRP was higher in group I (CRP: median 60.6 mg/l [IQR 41.2; 109.4]), than in group II (CRP: median 15.65 mg/l; IQR 10.4; 38.4), without a statistically significant difference (p=0.5), but the level of ferritin was significantly higher in group I (median 893.25 ng/ml [IQR 253.9; 7725.25]), than in group II (median 62.1 ng/ml [IQR 19.8; 211.8], p=0.009). Generally, we observed positive correlation between CRP and ferritine (r=0.629, р˂0.05), CRP and IL-18 (r=0.352, р˂0.05), CRP and IL1RA (r=0.693, р˂0.05); between ferritin and IL-18 (r=0.566, р˂0.05), between ferritin and IL1RA (r=0.545, р˂0.05). The strongest correlation was for ferritin and overall for groups I and II. We didn’t observe significantly difference between IP-10, IL1b, IL6 between groups. Conclusion Serum levels of IL-18 were elevated in the majority of pts with sJIA regardless of activity, but were significantly higher in pts with active disease and, especially, in pts with MAS. Increased level of IL-18 may reflect increased disease activity or development of MAS, that confirms the key role of IL-18 in sJIA and MAS. According to our data, in clinical practice the measure of serum level of ferritin more useful for early detecting MAS in pts with sJIA due to more stronger correlation between the levels of proinflammatory cytokines and ferritin, than between proinflammatory cytokines and CRP. We were unable to identify a statistically significant difference in the level of IL1RA in active sJIA and MAS, despite a significant correlation between the level of CRP and IL1RA, ferritin and IL1RA, which may be associated with small number of pts. Disclosure of Interests None declared